1. Field of the Invention
This invention provides a new chemical process for the production of 5-mercaptotetrazolyl-1-acetic acid which is used as an intermediate in the chemical production of antibacterial agents, e.g. cephalosporins such as ceforanide.
2. Description of the Prior Art
7-(2-Aminomethylphenylacetamido)-3-(1-carboxymethyltetrazol-5-ylthiomethyl) -3-cephem-4-carboxylic acid is a potent injectable cephalosporin having the generic name ceforanide; it has also been called BL-S786 in the literature. It was described, for example, in U.S. Pat. No. 4,100,346.
5-Mercaptotetrazolyl-1-acetic acid (1-carboxymethyl-5-mercaptotetrazole) is the 3-substituent in quite a few active antibiotics of the cephalosporin class, e.g., ceforanide ##STR1##
5-Mercaptotetrazolyl-1-acetic acid has been prepared by the following methods:
(a) Butylithiation of 1-methyl-5-mercaptotetrazole followed by reaction with carbon dioxide and acid hydrolysis. ##STR2##
(b) Reacting ethyl glycinate, carbon disulfide and sodium azide.
(c) Reacting 2-carboethoxymethyl isothiocyanate and sodium azide. All are described in detail in U.S. Pat. No. 4,100,346.
Bromination of 1-phenyl-tetrazole in carbon tetrachloride to product 5-bromo-1-phenyltetrazole was reported on page 295 by Stolle et al., J. Prakt. Chem. [2]134, 282-309 (1932). This reaction is apparently not mentioned in the corresponding Chemical Abstracts 26, 5565 (1932) but the page is cited as reference 95 on p. 40-42 of Heterocyclic Compounds, Vol. 8, Tetrazoles, Tetrazines and Purines and Related Ring Systems, Edited by R. C. Elderfield, John Wiley and Sons, Inc., New York (1967).
A brief review of the production of isothiouronium salts from various halides and their conversion to thiols has been provided at pages 186-191 of The Chemistry of the Thiol Group, Part 1, Edited by Saul Patai, John Wiley and Sons, New York (1974). On page 187 therein the cross-reference 94 refers to p. 32-35 of E. E. Reid, Chemistry of Bivalent Sulfur, Vol. 1, Chemical Publishing Co., New York (1958) on the same subject.
U.S. Pat. No. 3,468,874 describes the preparation of tetrazolyl-1-acetic acid in column 10 and of 5-bromo-1-tetrazolylacetic acid in column 16.
5-Mercapto-3-methyl-1,2,4-thiadiazole has been prepared by treatment with thiourea of the corresponding 5-chloro compound (U.S. Pat. No. 3,757,012, columns 5-6) and 2-mercapto-5-methyl-1,3,4-thiadiazole and 2-mercapto-5-hydroxymethyl-1,3,4-thiadiazole have been prepared by treatment with thiourea of the corresponding 5-bromo compounds (U.S. Pat. No. 3,907,786, columns 16 and 23; other preparations are given for other thiols.